University of Chicago
Type of paper: Thesis/Dissertation Chapter
Biohybrid devices. Biohybrid devices are implantable medical contraptions that undergo vascularization inside the body before the normal human cells (such as islet cells of Langerhans) can be placed inside them. They provide local immunosuppression that ensures that the normal human cells are not rejected by the host’s immune system or the graft versus host disease (Dorian).
Biohybrid devices can be used to prevent diseases such as liver failure and diabetes. For persons at risk of developing type I diabetes mellitus (such as genetically predisposed individuals) or pre-diabetic individuals, their islets cells of Langerhans can be protected by biohybrid devices (Ricchie).
These biohybrid devices are designed using nanoencapsulation technology into conformal polymer biomaterials that form a scaffold over the population of islet cells of Langerhans in the endocrine pancreas; thereby preventing the auto-antibodies from accessing the islets cells, and, causing irreversible injury to the cells by auto-immune reactions that ultimately lead to cell death, and, absolute lack of insulin production (Lucy et al). For the pre-diabetic individuals on immunomodulatory medications, the biohybrid scaffold locally concentrates the drug thus increasing its pharmacologic efficiency and reducing its systemic toxicity.
The biohybrid scaffold also improves nutrient distribution across the islet cells and reduces stress encountered by the islet cells of Langerhans (Nazek). Liver failure caused by autoimmune hepatitis can be prevented by biohybrid devices, which form an, intricate conformal scaffold on the hepatocytes surface thereby blocking the auto-antibodies from interacting with the hepatocytes, and, causing immune-mediated liver necrosis (Nazek).
Oxygen diffusion is critical for hybrid artificial organs because the normal human cells within them require oxygen for aerobic oxidative respiration and reduced oxygen diffusion may cause hypoxia (a form of cell injury) that leads to impaired physiological processes within the cells and ultimately to cell death(Lemburt et al). This necessitates that the biohybrid device be made of optimal design that allows adequate oxygen diffusion and consumption by the normal human cells (Dorian). These designs are based on experimental mathematical models (Provust).
The characteristics that influence the rate of oxygen diffusion across the biohybrid device are geometry (for instance, the spherical organoid biohybrid artificial liver [BAL] was observed to consume oxygen at rates that approximate normal hepatocytes oxygen consumption, while, the hollow tube model of BAL consumed oxygen at rates several magnitudes lower than normal hepatocytes), thickness of the biohybrid device(for instance, models of biohybrid blood vessels made up of hollow fiber scaffold exhibited correlation between increasing scaffold wall thickness and reduced oxygen perfusion) and permeability of the biohybrid device surface to oxygen. This oxygen permeability is a function of the intrinsic property of the polymer that is used to construct the scaffolds of the biohybrid device; also, the nanoencapsulation design influences oxygen permeability albeit to a smaller extent (Silvius).
There are several differences between intravascular and extra vascular biohybrid devices as explained below. Intravascular biohybrid devices are placed within the large blood vessels where they act as stents, or, they connect several blood vessels thereby acting as a biocompatible immunoprotective shunts; thus, the normal human cells within such devices obtain nourishment directly from the circulating blood. Extravascular biohybrid devices are placed outside the vascular compartment, for example, planar macro-capsules (extravascular devices) are placed in the peritoneal cavity; the normal human cells in these devices depend on diffusion to obtain the necessary nutrients and oxygen.
The extravascular devices are easily implantable and retrievable, but, the intravascular devices would need surgery in order to implant or retrieve them (Triavek). The geometry of biohybrid devices affects their efficiency because the normal human cells within them require an appropriate three-dimensional structure that maximizes the effective surface area in order to obtain adequate nutrition, oxygen and eliminate metabolic wastes. Geometry also influences the population of human cells that can be placed inside a biohybrid device. Geometry of biohybrid device also affects the interaction between the device and the human immune system (Nazek).